Theme 3:

Determinants of environmentally induced developmental mismatch



When the environment of early life is mismatched to the environment experienced later in life, our predictive adaptive response model would suggest there is a greater risk of disease. Our continuing series of studies in this theme address the nature and timing of the relevant exposures during the periconceptional to early postnatal period. Inducers of interest include nutrition, toxins and stressors, which may act indirectly on maternal or placental biology or on the fetus. There is increasing recognition that there are important interactions among these factors.


Work to date, particularly in the rodent and sheep, has focused on a range of early environmental cues, primarily nutritional, that have long-term physiological consequences. Critically we have found that the early cues do not necessarily induce the phenotype, but rather alter the sensitivity of the organism to later environments. We are undertaking studies to consider further the role of amplifying postnatal factors, such as rapid fat gain, in inducing mismatch.


Arguably, our recent work that has had the most impact and has the most potential is the finding that we can reverse developmental programming through a specific neonatal intervention in the rat. Thus we can now design experiments to compare induction and reversal in a search for basic mechanisms.


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Current projects


1. Epigenetic dynamics in developmental disease models


This is an experimental project that seeks to determine how maternal nutrition influences the developmental trajectory of the embryo, and whether increased disease risk is underpinned by epigenetic modifications early in life. This project involves the investigation of gene expression and the epigenetic regulation of specific cell populations within metabolic tissues (such as the liver), to determine whether the metabolic consequences of poor nutrition are cell-type specific.


Allan Sheppard

Project Leader: Dr Allan Sheppard (allan.sheppard <at>

Project team: Dr Anna Ponnampalam



2. Exposure to environmental chemicals and developmental origins of health and disease: Epigenetic regulation of the activities of key genes


This is an experimental project investigating how environmental chemicals that mimic estrogen can impact on the epigenetic regulation of genes related to metabolism, and whether the placenta is an effective barrier to fetal exposure to these agents. The project builds on technology developed with previous NRCGD funding that allows novel approaches to understanding placental function and the transfer of substances from maternal to fetal circulation.


Murray Mitchell     Ian Shaw

Project co-leaders:

Prof Murray Mitchell (left; m.mitchell <at> and

Prof Ian Shaw (right; <at>

Project team: Dr Allan Sheppard, Lisa Graham (PhD student)



3. Functional genomics of ageing and reproduction in the honeybee


This is an experimental project to provide an integrated understanding of how nutrition influences gene expression and life history traits. It combines evolutionary, ecological and developmental biology, and is underpinned by the observation that rate of reproduction is usually inversely related to longevity. This project focuses on the unusual case of honeybees, in which queens are both long-lived and massively fecund, while workers are both sterile and short-lived. This suggests that there might be no fundamental constraint that prevents animals from being both fecund and long-lived, and that the observed widespread negative correlation between these traits might represent a selective strategy.


David Raubenheimer     Peter Dearden

Project co-leaders:

Prof David Raubenheimer (left; d.raubenheimer <at> and Dr Peter Dearden (right; peter.dearden <at>

Project team: Sarah Morgan (PhD student)



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